The G-protein coupled receptor 83 GPR83 is an orphan G-protein coupled receptor for which the natural ligands and signaling pathways remain to be identified. Previous studies suggest a role of GPR83 in the regulation of thermogenesis and the control of circulating adiponectin. The aim of this study was to gain insights into the molecular underpinnings underlying GPR83 signaling. In particular, we aimed to assess the underlying G-protein activated signaling pathway of GPR83 and how this pathway is affected by mutational activation and zincII challenge. Finally, we assessed the capacity of GPR83 for homodimerization. Our results show for the first time that mouse m GPR83 has high basal Gq-11 activity without affecting Gi or Gs signaling. Furthermore, we found that, under physiological conditions, zincII but not calciumII and magnesiumII potently activates mGPR83, thus identifying zincII as an endogenous molecule with agonistic capability to activate mGPR83. In line with the observation that zincII-ions activate mGPR83, we identified a cluster of ion-binding sensitive amino acids e.g. His145, His204, Cys207, Glu217 in an activation sensitive receptor region of mGPR83. The occurrence of a constitutive activating mutant and a zincII-binding residue at the N-terminal part corroborate the importance of this region in mGPR83 signal regulation. Finally, our results indicate that mGPR83 forms homodimers, which extend the current knowledge and molecular facets of GPR83 signaling.